Reassessment of the Role of Aromatic Amino Acid Hydroxylases and the Effect of Infection by Toxoplasma gondii on Host Dopamine
Reassessment of the Role of Aromatic Amino Acid Hydroxylases and the Effect of Infection by Toxoplasma gondii on Host Dopamine
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DOI：
10.1128/iai.02465-14
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发表时间：
2015-03-01
影响因子：
3.1
通讯作者：
Sibley, L. David
中科院分区：
文献类型：
--
作者：
Wang, Zi T.;Harmon, Steve;Sibley, L. David
先前已经描述过弓形虫感染会导致受感染的小鼠失去对猫尿的恐惧。这种行为操纵被认为涉及由寄生虫编码的芳香氨基酸羟化酶引起的宿主多巴胺途径的改变。在这里，我们报告了芳香氨基酸羟化酶 AAH2 基因的成功敲除和互补，在体外和体内寄生虫生长或分化中没有观察到表型。此外，两种芳香族氨基酸羟化酶的表达水平在速殖子和缓殖子中都是可以忽略不计的。最后，即使使用 BAG1 启动子过表达 AAH2，我们也无法在体外或体内证实先前描述的寄生虫感染对宿主多巴胺的影响。总之，这些数据表明，寄生虫中的 AAH 酶不会引起宿主大脑中多巴胺的整体或区域性改变，尽管它们可能会局部影响该途径。此外，我们的研究结果表明 AHH 酶在弓形虫中具有替代作用，因为 AAH1 对于非多巴胺能细胞的生长至关重要。
Toxoplasma gondii infection has been described previously to cause infected mice to lose their fear of cat urine. This behavioral manipulation has been proposed to involve alterations of host dopamine pathways due to parasite-encoded aromatic amino acid hydroxylases. Here, we report successful knockout and complementation of the aromatic amino acid hydroxylase AAH2 gene, with no observable phenotype in parasite growth or differentiation in vitro and in vivo. Additionally, expression levels of the two aromatic amino acid hydroxylases were negligible both in tachyzoites and in bradyzoites. Finally, we were unable to confirm previously described effects of parasite infection on host dopamine either in vitro or in vivo, even when AAH2 was overexpressed using the BAG1 promoter. Together, these data indicate that AAH enzymes in the parasite do not cause global or regional alterations of dopamine in the host brain, although they may affect this pathway locally. Additionally, our findings suggest alternative roles for the AHH enzymes in T. gondii, since AAH1 is essential for growth in nondopaminergic cells.